a Department of Molecular Biology and Genetics , İzmir Institute of Technology , Urla , İzmir , Turkey and.
b Faculty of Life and Natural Sciences , Abdullah Gul University , Kayseri , Turkey.
Crit Rev Biotechnol. 2016 Aug;36(4):716-26. doi: 10.3109/07388551.2015.1015957. Epub 2015 Mar 11.
Chemotherapy is the main strategy for the treatment of cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance. The resistance can be intrinsic or acquired. The resistance phenotype is associated with the tumor cells that gain a cross-resistance to a large range of drugs that are structurally and functionally different. Multidrug resistance arises via many unrelated mechanisms, such as overexpression of energy-dependent efflux proteins, decrease in uptake of the agents, increase or alteration in drug targets, modification of cell cycle checkpoints, inactivation of the agents, compartmentalization of the agents, inhibition of apoptosis and aberrant bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and molecular and biochemical approaches to overcome multidrug resistance have been a major goal in cancer research. This review comprises the mechanisms guiding multidrug resistance in cancer chemotherapy and also touches on approaches for reversing the resistance.
化疗是癌症治疗的主要策略。然而，限制化疗成功的主要问题是多药耐药的发展。耐药性可以是内在的或获得的。耐药表型与肿瘤细胞有关，这些细胞对结构和功能不同的大量药物获得交叉耐药性。多药耐药性通过许多不相关的机制产生，例如能量依赖性外排蛋白的过度表达、药物摄取减少、药物靶点增加或改变、细胞周期检查点的改变、药物失活、药物区室化、凋亡抑制和异常生物活性鞘脂代谢。确切阐明耐药机制和克服多药耐药性的分子和生化方法一直是癌症研究的主要目标。本综述包括指导癌症化疗中多药耐药性的机制，并涉及逆转耐药性的方法。
